The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

FKBP6  -  FK506 binding protein 6, 36kDa

Homo sapiens

Synonyms: 36 kDa FK506-binding protein, 36 kDa FKBP, FK506-binding protein 6, FKBP-36, FKBP-6, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of FKBP6

  • A novel human gene FKBP6 is deleted in Williams syndrome [1].
  • Hemizygous deletion of FKBP6 may contribute to certain defects such as hypercalcemia and growth delay in WS [1].
  • The human cyclophilin hCyp-18, an abundant peptidyl-prolyl cis-trans isomerase (PPIase) implicated in protein folding, controls the infection of CD4(+) T-cells by HIV-1, the pathologic agent of AIDS [2].
  • In conclusion, our results suggest that genetic defects in FKBP6 can be excluded as a common cause of azoospermia in humans [3].
  • The prokaryotic peptidyl-prolyl cis-trans-isomerase called "rotamase", a homolog of the human cyclophilin, has been identified in Escherichia coli [4].

High impact information on FKBP6

  • FK506 and rapamycin strongly inhibit the peptidyl-prolyl cis-trans isomerase activity of FKBP, whereas cyclosporin A inhibits that of cyclophilin [5].
  • Although unrelated at the amino-acid sequence level, they both possess peptidyl-prolyl cis-trans isomerase activities which are inhibited by immunosuppressants that block signal transduction pathways leading to T-lymphocyte activation [5].
  • By measuring the rate of chymotrypsin cleavage of the substrate succinyl-Ala-Ala-Pro-Phe p-nitroanilide, we found that the fusion protein had rotamase activity comparable to that of human FK506-binding protein [6].
  • By spheroplast fractionation of cells harboring the expression vector for the complete rot gene, the rotamase is located in the periplasm, where it could function in refolding of secreted proteins [4].
  • Cyclophilins comprise a highly conserved family of proteins which are the primary targets of the potent immunosuppressive drug, cyclosporin A (CsA), and which display peptidyl prolyl cis-trans-isomerase (PPIase) activity [7].

Biological context of FKBP6

  • FKBP6 shows homology to the FK-506 binding protein (FKBP) class of immunophilins [1].
  • FKBP6 consists of nine exons and is completely contained within a 35-kb cosmid clone [1].
  • The purified protein showed PPIase activity and its activity was inhibited by FK506 with an IC50 of 7 microM [8].
  • In this study, we show that macrophage-tropic and T-cell-tropic V3 loop peptides bind specifically to the active site of the immunophilins FK506-binding protein (FKBP12), and cyclophilins A and B. Macrophage-tropic and T-cell-tropic V3 loop peptides inhibited the peptidyl-prolyl cis-trans isomerase (PPIase) activities of the immunophilins [9].
  • Mutations in the chromosome pairing gene FKBP6 are not a common cause of non-obstructive azoospermia [3].

Anatomical context of FKBP6

  • FKBP6 is expressed in testis, heart, skeletal muscle, liver, and kidney [1].
  • The expression of the human FKBP6 gene was specific to the testis, and a novel polymorphism site, 245C --> G (Y60X) could be found in exon 3 [10].
  • The PPIase was associated with the outside of sonicated submitochondrial particles but dissociated in 0.5 M NaCl [11].
  • When mitochondria were treated with increasing concentrations of digitonin, the 21-kDa PPIase fractionated with the matrix marker enzyme, malate dehydrogenase [11].
  • FKBP60 contains a hydrophobic signal peptide at the N-terminus, 4 peptidyl-prolyl cis/trans isomerase (PPIase) domains and an endoplasmic reticulum retention motif (HDEL) at the C-terminus [12].

Associations of FKBP6 with chemical compounds

  • Based on the chymotrypsin-coupled assay using the tetrapeptide substrate succinyl-Ala-Ala-Pro-Phe-p-nitroanilide, the purified protein has rotamase activity identical to human cyclophilin with a catalytic efficiency close to the upper diffusional limit (kcat/Km approximately 1.0 x 10(7) M-1 x S-1 at 10 degrees C) [4].
  • Due to the low equilibrium population of the X-cis-Pro-Phe-pNA isomer (the PPIase substrate), in conjunction with the low solubility of p-nitroaniline generated by chymotrypsin hydrolysis, substrate concentrations in the saturating region are not experimentally attainable [13].
  • The PPIase catalysis toward the substrate Suc-Ala-Phe-Pro-Phe-pNA has been studied by 1H NMR spectroscopy [14].
  • Wheat (Triticum aestivum L.) FKBP73 (wFKBP73) is a peptidyl-prolyl cis-trans isomerase belonging to the FK506-binding protein (FKBP) family [15].

Other interactions of FKBP6


Analytical, diagnostic and therapeutic context of FKBP6

  • Fluorescence in situ hybridization experiments show that FKBP6 gene is deleted in 40/40 WS individuals [1].
  • FKBP12, and cyclophilins A and B were found to be present in normal human blood in the ranges 0.8-1.7, 1.4-2.3 and 2.4-3.1 nM, respectively, as demonstrated by PPIase activity measurements and western blot analysis [9].


  1. A novel human gene FKBP6 is deleted in Williams syndrome. Meng, X., Lu, X., Morris, C.A., Keating, M.T. Genomics (1998) [Pubmed]
  2. Synthesis and evaluation of Glypsi(PO(2)R-N)Pro-containing pseudopeptides as novel inhibitors of the human cyclophilin hCyp-18. Demange, L., Moutiez, M., Dugave, C. J. Med. Chem. (2002) [Pubmed]
  3. Mutations in the chromosome pairing gene FKBP6 are not a common cause of non-obstructive azoospermia. Westerveld, G.H., Repping, S., Lombardi, M.P., van der Veen, F. Mol. Hum. Reprod. (2005) [Pubmed]
  4. Peptidyl-prolyl cis-trans-isomerase from Escherichia coli: a periplasmic homolog of cyclophilin that is not inhibited by cyclosporin A. Liu, J., Walsh, C.T. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  5. Solution structure of the major binding protein for the immunosuppressant FK506. Moore, J.M., Peattie, D.A., Fitzgibbon, M.J., Thomson, J.A. Nature (1991) [Pubmed]
  6. Neisseria meningitidis encodes an FK506-inhibitable rotamase. Sampson, B.A., Gotschlich, E.C. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  7. Retina-specifically expressed novel subtypes of bovine cyclophilin. Ferreira, P.A., Hom, J.T., Pak, W.L. J. Biol. Chem. (1995) [Pubmed]
  8. FKBP-type peptidyl-prolyl cis-trans isomerase from a sulfur-dependent hyperthermophilic archaeon, Thermococcus sp. KS-1. Iida, T., Furutani, M., Nishida, F., Maruyama, T. Gene (1998) [Pubmed]
  9. The V3 loop of human immunodeficiency virus type-1 envelope protein is a high-affinity ligand for immunophilins present in human blood. Endrich, M.M., Gehring, H. Eur. J. Biochem. (1998) [Pubmed]
  10. Is a genetic defect in Fkbp6 a common cause of azoospermia in humans? Miyamato, T., Sato, H., Yogev, L., Kleiman, S., Namiki, M., Koh, E., Sakugawa, N., Hayashi, H., Ishikawa, M., Lamb, D.J., Sengoku, K. Cell. Mol. Biol. Lett. (2006) [Pubmed]
  11. Involvement of cyclophilin D in the activation of a mitochondrial pore by Ca2+ and oxidant stress. Tanveer, A., Virji, S., Andreeva, L., Totty, N.F., Hsuan, J.J., Ward, J.M., Crompton, M. Eur. J. Biochem. (1996) [Pubmed]
  12. Biochemical analysis of mouse FKBP60, a novel member of the FKPB family. Shadidy, M., Caubit, X., Olsen, R., Seternes, O.M., Moens, U., Krauss, S. Biochim. Biophys. Acta (1999) [Pubmed]
  13. Determination of kinetic constants for peptidyl prolyl cis-trans isomerases by an improved spectrophotometric assay. Kofron, J.L., Kuzmic, P., Kishore, V., Colón-Bonilla, E., Rich, D.H. Biochemistry (1991) [Pubmed]
  14. Peptidyl-prolyl cis-trans isomerase activity as studied by dynamic proton NMR spectroscopy. Hübner, D., Drakenberg, T., Forsén, S., Fischer, G. FEBS Lett. (1991) [Pubmed]
  15. Wheat FKBP73 functions in vitro as a molecular chaperone independently of its peptidyl prolyl cis-trans isomerase activity. Kurek, I., Pirkl, F., Fischer, E., Buchner, J., Breiman, A. Planta (2002) [Pubmed]
  16. Separation and identification of differentially expressed nuclear matrix proteins between human esophageal immortalized and carcinomatous cell lines. Xiong, X.D., Li, E.M., Xu, L.Y., Chen, H.B., Chen, L., Cai, W.J., Han, Y.L., Shen, Z.Y., Zeng, Y. World J. Gastroenterol. (2003) [Pubmed]
WikiGenes - Universities